The pathobiochemistry of hereditary pancreatitis:: Studies on recombinant human cationic trypsinogen

Background/Aims: This study attempts to identify the biochemical alterations in human cationic trypsinogen and trypsin caused by the hereditary pancreatitis-associated mutations Arg117 --> His and Asn21 --> IIe. Methods:, Recombinant wild-type and mutant human cationic trypsinogens were expressed in Escherichia coli and purified to homogeneity, and trypsin autolysis and trypsinogen autoactivation were characterized. Results: Both mutations significantly enhanced the autoactivation of human cationic trypsinogen. In addition, the Arg117 --> His mutation inhibited autocatalytic inactivation of trypsin, while the Asn21 --> IIe mutation had no such effect. Conclusions: The findings support the notion that enhanced trypsinogen activation in the pancreas is the common: initiating step in hereditary pancreatitis, whereas trypsin stabilization plays a role in cases associated with the Arg117 --> His mutation. Copyright (C) 2001 S. Karger AG, Basel and IAP.